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 Previous Article
Journal of Neuroscience, Vol 16, 1957-1963, Copyright © 1996 by Society for Neuroscience
Relapse to heroin-seeking in rats under opioid maintenance: the effects of stress, heroin priming, and withdrawal
Y Shaham, H Rajabi and J Stewart
Department of Psychology, Concordia University, Montreal, Quebec, Canada.
It is widely believed that opioid withdrawal symptoms contribute to relapse
to opioid use, but relapse is highly probable in experienced users even
after prolonged abstinence and during opioid maintenance therapy. We have
found using an animal model of relapse, the reinstatement procedure, that
the two events that reliably reinstate heroin-seeking behavior are
reexposure to heroin, and brief exposure to footshock stress. Contrary to
expectation, opioid antagonist-induced withdrawal does not reinstate
heroin-seeking. We now report on reinstatement of heroin-seeking in rats
trained to self-administer heroin and subsequently exposed to a maintenance
dose of heroin via minipump and allowed to self-administer saline. With the
minipump in, naloxone-induced withdrawal did not reinstate drug-seeking, a
priming injection on heroin was only mildly effective, and footshock was
highly effective. Twenty-four hours after removal of the minipump
(spontaneous withdrawal), animals reinitiated heroin-seeking and,
subsequently, both heroin and footshock reinstated heroin-seeking. In
summary, brief exposure to stress reinstated heroin-seeking in both
heroin-maintained and withdrawn animals. The heroin prime reliably
reinstated drug- seeking only in the absence of the minipump; opioid
"withdrawal," as such, did not reinstate drug-seeking behavior. Naloxone
given to heroin- maintained animals induced withdrawal symptoms, caused a
mild depression in the levels of dopamine and its metabolites in the
nucleus accumbens septi (NAS), but did not reinstate drug-seeking.
Reinstatement of heroin-seeking during spontaneous withdrawal was not
accompanied by reductions in basal dopamine and its metabolites in NAS.
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